Journal ArticleDOI
Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia.
TLDR
It is shown that metformin increased AMPK activity in microglial cells and that all observed effects are AMPK-dependent because the pretreatment of microglia with compound C reversed the effects of the drug.Abstract:
Recent evidence suggests that metformin shows beneficial effects in experimental models of neuroinflammatory diseases. The aim of the present study was to determine the effect of metformin on phagocytosis and acidification of lysosomal/endosomal compartments in rat primary microglia in the presence of lipopolysaccharide (LPS) and/or beta-peptides (25–35), (1–40), and (1–42). Metformin increased the phagocytosis of fluorescent microspheres in the presence or absence of all the beta-peptides. However, the drug had no effect on the phagocytosis in LPS-stimulated microglia regardless of the presence of all the beta-peptides. Metformin acidified the lysosomal/endosomal compartments in the presence or absence of the beta-peptide 1–40 in both resting and activated microglia. To elucidate the mechanism of metformin action, we used 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside as an activator of adenosine monophosphate-activated protein kinase (AMPK) and compound C as a confirmed pharmacological inhibitor of AMPK. We have shown that metformin increased AMPK activity in microglial cells and that all observed effects are AMPK-dependent because the pretreatment of microglia with compound C reversed the effects of the drug. Since degradation of proteins in lysosomal/endosomal compartments depends largely on their phagocytosis and acidification, metformin may be beneficial in proteinopathies affecting the brain.read more
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Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide
Krzysztof Łabuzek,Dariusz Suchy,Bożena Gabryel,Anna M. Bielecka,Sebastian Liber,Bogusław Okopień +5 more
TL;DR: It is concluded that orally-dosed metformin rapidly crosses the blood-brain barrier and differently accumulates in structures of the central nervous system.
Journal ArticleDOI
Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
Mi-Hyang Cho,Kwangmin Cho,Hoe-Jin Kang,Eun-Young Jeon,Hun-Sik Kim,Hyung-Joon Kwon,Hong-Mi Kim,Dong-Hou Kim,Seung-Yong Yoon +8 more
TL;DR: A novel role for autophagy is demonstrated in the clearance of extracellular Aβ fibrils by microglia and in the regulation of the Aβ-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome usingmicroglia specific atg7 knockout mice and cell cultures.
Journal ArticleDOI
Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice.
Zhenri Ou,Xuejian Kong,Xiangdong Sun,Xiaosong He,Le Zhang,Zhuo Gong,Jingyi Huang,Biao Xu,Dahong Long,Jianhua Li,Qingqing Li,Liping Xu,Aiguo Xuan +12 more
TL;DR: The data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AM PK/P65 NF-κB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.
Journal ArticleDOI
AMP-activated protein kinase: a potential player in Alzheimer's disease.
TL;DR: In this paper, the potential role of AMPK function in respect to various aspects affecting Alzheimer's disease pathogenesis is outlined. But, the responses of AMP activation are dependent on stimulation and the extent of activating stress.
Journal ArticleDOI
CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents
Raffaela Cipriani,Pia Villa,Giuseppina Chece,Clotilde Lauro,Alessandra Paladini,Edoardo Micotti,Carlo Perego,Maria Grazia De Simoni,Bertil B. Fredholm,Fabrizio Eusebi,Cristina Limatola +10 more
TL;DR: It is suggested that acute administration of CX3CL1 reduces ischemic damage via an adenosine-dependent mechanism and that the absence of constitutive CX2CL1–CX3CR1 signaling changes the outcome of microglia-mediated effects during CX 3CL1 administration to ischeMIC brain.
References
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